A MICROFLUIDIC DETECTION DEVICE WITH IMMOBILIZED BIOCHEMICAL ASSAYS, FABRICATION OF SAME AND METHOD OF ANALYSING A FLUID SAMPLE

Abstract

The invention relates to a microfluidic chip with specifically shaped chambers to improve operability. The present invention further relates to a method of manufacturing a microfluidic chip, which has reagents embedded inside and which can perform analysis of multiple target analytes from a single test sample. Further, the invention relates to a simple analysis system that can be used by non-technical users by automating several stages of the process and providing the end user with simple feedback.

Claims

1. A microfluidic chip comprising: an inlet; at least one fluid path comprising at least one fluidic channel from the inlet to an outlet, said at least one fluidic path comprising a detection chamber and optionally a reaction chamber between the inlet and the detection chamber; said at least one fluidic path being enclosed and configured to allow a fluid sample dispensed onto the inlet to move through fluidic channels to at least one detection chamber surface due to capillary motion, characterised in that the outlet contains a vent to enable capillarity, said outlet being adjacent to the detection chamber and positioned substantially opposite to where the fluidic channel enters the detection chamber.

2. The microfluidic chip of claim 1, wherein the detection chamber surface is aligned with an inspection window, and wherein the outlet and vent does not overlap with the inspection window.

3. The microfluidic chip of claim 1 or claim 2, wherein the transitional zone between the fluidic channel and the detection chamber is filleted.

4. The microfluidic chip of claim 3, wherein the fillets have a curve with a radius of from 3 mm to 7 mm.

5. A microfluidic chip comprising: an inlet; at least one fluid path comprising at least one fluidic channel from the inlet to a detection chamber, said at least one fluid path comprising a reaction chamber between the inlet and the detection chamber; characterised in that the reaction chamber is shaped with an aspect ratio of 3:2 or higher.

6. The microfluidic chip according to claim 5, wherein the fluid path is enclosed, said reaction chamber having a depth of from 500 to 1500 μm, the floor of the reaction chamber contains grooves orthogonal to the flow direction, wherein the grooves have a width of from 10 to 150 μm, and a depth of from 20 to 200 μm.

7. The microfluidic chip according to claim 5 or claim 6, wherein the reaction chamber is shaped as an oval.

8. The microfluidic chip according to any of claims 5 to 7, wherein the width of the reaction chamber is from 2 to 5 mm.

9. The microfluidic chip according to any one of claims 5 to 8, wherein the aspect ratio of the reaction chamber is 2:1 or higher.

10. A method of fabricating a microfluidic chip (1), particularly a microfluidic chip according to any preceding claim, comprising at least one fluid path from an inlet (2), through at least one fluidic channel (7) and to an outlet (6), the method comprising: providing a plurality of layers (3, 4, 5), which are initially separated, each of the layers in the plurality of layers (3, 4, 5) being made of at least one polymeric material, each of the plurality of layers (3, 4, 5) being substantially shaped as a rectangular cuboid having two opposite surfaces, which are significantly larger than other surfaces of the layer, wherein at least one layer of the plurality of layers (3, 4, 5) comprises an adhesive on both of its larger surfaces, ensuring that enough layers comprise an adhesive such that when the plurality of layers (3, 4, 5) are assembled at a later time at least one of any two larger surfaces facing each other comprises an adhesive, providing the inlet (2) in one of the plurality of layers (3, 4, 5), providing at least one outlet (6) in a larger surface of one of the plurality of layers (3, 4, 5), providing at least one layer of the plurality of layers (3, 4, 5) with one or more fluidic channels (7), where providing a layer with fluidic channels (7) comprises at least one of: engraving a channel structure onto one or both of the larger surfaces of the layer, and/or cutting a channel structure by cutting throughgoing channels in the larger surfaces of the layer, and/or cutting a fluidic passage hole by cutting a throughgoing hole in the larger surfaces of the layer thus creating a fluidic channel that allows fluid to flow from one layer to another, optionally, creating at least one reaction chamber surface (8) by at least one of: engraving on a larger surface of at least one layer of the plurality of layers (3, 4, 5) to make an indentation and/or a pattern, and/or cutting a fluidic passage hole in a larger surface of at least one layer of the plurality of layers, whereby the fluidic passage hole cut-out will define a reaction chamber surface on an adjacent layer after assembly of the plurality of layers, creating at least one detection chamber surface (9) by at least one of: engraving on a larger surface of at least one layer of the plurality of layers (3, 4, 5) to make an indentation and/or a pattern, and/or cutting a fluidic passage hole in a larger surface of at least one layer of the plurality of layers, whereby the fluidic passage hole cut-out will define a detection chamber surface on an adjacent layer after assembly of the plurality of layers, preparing at least one of the reaction chamber surfaces (8), if present, and/or at least one of the detection chamber surfaces (9), wherein preparing a reaction chamber surface (8) and/or a detection chamber surface (9) comprises: dispensing at least one reagent onto the reaction chamber surface (8) and/or detection chamber surface (9), subsequently, if required to immobilize the dispensed reagent, drying and/or ventilating the reaction chamber surface (8) and/or detection chamber surface (9), assembling the plurality of layers (3, 4, 5), where assembling the plurality of layers (3, 4, 5) comprises stacking the layers in the plurality of layers (3, 4, 5) on top of each other with a larger surface of one layer aligning with a larger surface of another layer, such that: the inlet (2) is not covered, at least one of any two larger surfaces facing each other comprises an adhesive, at least one outlet (6) aligns with a detection chamber surface (9), the outlet (6) allowing electromagnetic radiation emitted from the detection chamber surface to leave the microfluidic chip (1), the at least one fluid path is provided by aligning the inlet (2), fluidic channel(s) (7), reaction chamber surface(s) (8), if present, detection chamber surface(s) (9) and outlet(s) (6) such that the at least one fluid path further extends to one of the at least one detection chamber surfaces (9), the at least one fluid path will allow a fluid sample dispensed onto the inlet (2) to move through fluidic channels (7) to at least one detection chamber surface (9) due to capillary motion, and bonding the plurality of layers (4, 5, 6) together.

11. A method of fabricating a microfluidic chip according to claim 10, wherein the floor of the reaction and/or detection chamber contains grooves having a width of from 10 to 150 μm, and a depth of from 20 to 200 μm.

12. A method of fabricating a microfluidic chip according to claim 11, wherein the grooves are orthogonal to the flow direction.

13. A method of fabricating a microfluidic chip (1) according to any of claims 10 to claim 12, the method further comprising providing an identifier to the microfluidic chip (1), where the identifier is detectable by visual inspection or other types of inspection.

14. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 13, wherein the adhesive is an acrylic adhesive.

15. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 14, wherein the at least one layer comprising one or more fluidic channels (7) is made of polyethylene terephthalate (PET) or poly(methyl methacrylate) (PMMA).

16. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 15, wherein each of the layers in the plurality of layers (3, 4, 5) provided are made of at least one of: a thermosetting polymer and/or a thermoplastic polymer and/or an elastomer and/or a glass and/or quartz.

17. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 16, wherein a layer comprising at least one reaction chamber surface (8) and/or at least one detection chamber surface (9) is made of a different polymeric material than a layer comprising one or more fluidic channels (7).

18. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 17, wherein at least one of the patterns engraved to provide a reaction chamber surface (8) and/or a detection chamber surface (9) increases the binding affinity for a reagent to be dispensed thereupon.

19. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 18, wherein the inlet (2) is cut or engraved in a droplet shape, trapezoidal shape, triangular shape or any other tapering geometrical shape.

20. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 19, wherein the at least one reagent dispensed onto a reaction chamber surface (8) and/or a detection chamber surface (9) is at least one of: an enzyme, and/or a substrate for enzymatic reactions, and/or an antibody, and/or an antigen, and/or an aptamer, and/or an ELISA assay, and/or redox reaction reagents, and/or polymeric membranes, such as ion-selective membranes made using polymer and plasticizer, and/or nanoparticles, such as liposomes and transferosomes.

21. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 19, wherein providing a layer with one or more fluidic channels (7) further comprises providing a zig-zag shape (10) to a part of or the whole of one or more of the fluidic channels (7).

22. A method of fabricating a microfluidic chip (1) according to any of claims 10 to 22, the method further comprising modifying at least one of the reaction chamber surfaces (8) and/or detection chamber surfaces (9) by at least one of the processes of: laser patterning, and/or chemical treatment, such as e.g. coating, immersion in a solvent, incubation in a solvent, and/or exposure to UV radiation.

23. A microfluidic chip according to any of claims 1 to 9, as made by a method according to any of claims 10 to 22.

24. A microfluidic chip (1), wherein the microfluidic chip (1) is obtained using the method according to any one of claims 10 to 22.

25. A microfluidic system comprising: a microfluidic chip (1) according to any of claim 1 to 9 or 24, or as obtained using the method according to any one of claims 10-22, an analysis device (11), the analysis device (11) comprising: a barcode scanner (12), a microfluidic chip inlet (13), where the microfluidic chip inlet (13) is suitable for insertion of the microfluidic chip (1) into the analysis device (11), an optical sensor, a lens array, one or more light sources, an optical filter, a display screen, a power supplying element.

26. A method for analysing a fluid sample, comprising: providing a microfluidic chip (1)) according to any of claim 1 to 9 or 24, or as obtained using the method according to any one of claims 10-22, providing the fluid sample at the inlet (2) of the microfluidic chip (1), measuring, subsequent to providing the fluid sample at the inlet (2), electromagnetic radiation emitted from one or more of the detection chamber surfaces. 27. A method as defined in claim 26, wherein the fluid sample contains 0.5 to 1.5 wt % polysorbate.

28. Use of a non-ionic surfactant, particularly a polysorbate, to increase the rate of capillary flow in a microfluidic chip.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0217] The invention will now be described in more detail with regard to the accompanying figures. The figures show one way of implementing the present invention and is not to be construed as being limiting to other possible embodiments falling within the scope of the attached claim set.

[0218] FIG. 1 shows schematically a plurality of layers used in the fabrication of a microfluidic chip according to an embodiment of the present invention.

[0219] FIG. 2 shows a side view of the plurality of layers from FIG. 1.

[0220] FIG. 3 shows a schematic illustration of a microfluidic chip according to an embodiment of the present invention. The illustration shows features, which would not necessarily be visible to the naked eye after fabrication of the microfluidic chip.

[0221] FIG. 4 shows a schematic illustration of a microfluidic chip according to an embodiment of the present invention. The illustration shows features, which would not necessarily be visible to the naked eye after fabrication of the microfluidic chip.

[0222] FIG. 5 shows a closer view of parts of the microfluidic chip in FIG. 4.

[0223] FIG. 6A and 6B each show schematically an example of a plurality of layers used in embodiments of the present invention to fabricate a microfluidic chip. FIG. 6A shows three layers, while FIG. 6B shows four layers.

[0224] FIG. 7 shows schematically a side view of an analysis device.

[0225] FIG. 8 shows schematically a syringe for use in providing a fluid sample to the inlet of a microfluidic chip.

[0226] FIG. 9 is a flow-chart of a method according to the invention.

[0227] FIG. 10 is a flow-chart of a method according to the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

[0228] FIG. 1 and FIG. 2 show schematically a plurality of layers 3, 4, 5 used in the method of fabrication of a microfluidic chip 1 according to an embodiment of the present invention. Each of the layers in the plurality of layers 3, 4, 5 is substantially shaped as a rectangular cuboid having two opposite surfaces, which are significantly larger than other surfaces of the layer.

[0229] A base layer 5 made of a polymeric material is provided. The base layer may be made of a material and/or have a finish, which makes it easier for a user to handle the microfluidic chip. One or more detection chamber surfaces 9 and, optionally, one or more reaction chamber surfaces 8 are provided by making an indentation and/or pattern in the base layer 5. The indentation and/or pattern may be made by laser engraving. Advantageously, the base layer 5 may be made of PMMA acrylic, which functions both as a stable support for a user when holding the chip and as an inert medium on which to dispense one or more reagents onto.

[0230] The reaction chamber surface(s) 8, if present, and/or the at least one detection chamber surface 9 is prepared by: [0231] dispensing at least one reagent onto the reaction chamber surface 8 and/or detection chamber surface 9, [0232] subsequently, if required to immobilize the dispensed reagent, drying and/or ventilating the reaction chamber surface 8 and/or detection chamber surface 9.

[0233] In some embodiments, only the detection chamber surface comprises at least one reagent, while in other embodiments one or more reaction chamber surfaces located upstream from the detection chamber will also comprise at least one reagent.

[0234] In the embodiment in FIG. 1, the base layer therefore also functions as a reagent carrier layer, i.e. a layer on which at least one reagent is dispensed. In another embodiment, the reagent carrier layer is not the base layer.

[0235] In FIG. 1, a fluidic channel layer 4 made of a polymeric material is provided. A possible choice for the polymeric material is a composite sandwich material having PET or PMMA in the middle being sandwiched by an acrylic adhesive on both sides. This allows for a thin layer, while providing rigidity and integrity of the fluidic channel(s).

[0236] The fluidic channel layer 4 comprises one or more fluidic channels 7, which function to transport fluid through the microfluidic chip 1. The one or more fluidic channel(s) 7 are provided as a combination of: [0237] engraving a channel structure onto a larger surface of the fluidic channel layer 4, and/or [0238] cutting throughgoing channels in the larger surfaces of the layer, and/or [0239] cutting one or more fluidic passage holes as a throughgoing hole cut in the larger surfaces of the layer.

[0240] A fluidic passage hole is thus a fluidic channel that allows fluid to flow from one layer to another.

[0241] It is also possible for the reagent carrier layer and fluidic channel layer to be the same layer.

[0242] In FIG. 1, a capping layer 3 made of a polymeric material is provided. An inlet 2 and one or more outlets 6 is provided in the capping layer. The outlets may be of any suitable shape and size and act as vents, which enables capillarity.

[0243] In other possible designs, the inlet 2 is provided in the base layer, a reagent carrier layer or a fluidic channel layer.

[0244] Subsequent to preparation of the reaction chamber surface(s), if present, and detection chamber surface(s), the plurality of layers 3, 4, 5 is assembled by stacking the layers in the plurality of layers 3, 4, 5 on top of each other with a larger surface of one layer aligning with a larger surface of another layer. In the embodiment shown in FIG. 1, the fluidic channel layer could advantageously be made of a composite sandwich material as described above.

[0245] The one or more outlets 6 align with the one or more detection chamber surface(s) 9 in the reagent carrier layer as well as with any cut-through in intermediate layers necessary to ensure that any electromagnetic radiation emitted from a detection chamber surface 9 can leave the microfluidic chip 1. The electromagnetic radiation typically leaves through an inspection window, with the outlets and outlet vents desirably being positioned away from the detection chamber surfaces.

[0246] At least one fluid path is provided as the inlet 2, fluidic channel(s) 7, reaction chamber surface(s) 8, if present, detection chamber surface(s) 9 and outlet(s) 6 are aligned. When the layers of the plurality of layers 3, 4, 5 are assembled and bonded the at least one fluid path is formed as the fluidic channel(s) 7 are sealed by the adjacent layer(s). Likewise, as the detection chamber surface(s) 9 are partly enclosed by adjacent layers, detection chamber(s) are formed in such a way that fluid may enter and exit the detection chamber(s). Equally, any reaction chamber surface(s) 8 are partly enclosed by adjacent layers, creating reaction chamber(s) in such a way that fluid may enter and exit the reaction chamber(s).

[0247] This provides at least one fluid path extending from the inlet 2, through at least one fluidic channel 7, optionally past at least one reaction chamber upstream from any detection chamber, to one of the at least one detection chambers and to an outlet 6. The at least one fluid path will allow a fluid sample dispensed onto the inlet 2 to move through fluidic channel(s) 7 to at least one detection chamber 9 due to capillary motion.

[0248] In the embodiment shown in FIG. 1, where the fluidic channel layer 4 advantageously may be made of a composite sandwich material with adhesive on both of the larger surfaces, bonding is done by heating of the assembled plurality of layers. The heating may be done by using a lamination device on low heat.

[0249] In other designs, bonding of the layers in the plurality of layers 3, 4, 5 may be achieved by e.g. ultrasonic welding, chemical welding, adhesive material coating or other intrinsic material properties.

[0250] In some designs, the capping layer further comprises an identifier. The identifier may be an engraving in the capping layer.

[0251] In FIG. 1 is shown a chamber 35, which is not connected to the fluidic path. This is a chamber, which is unused in the embodiment shown in FIG. 1, but which may be connected to the fluidic path in another embodiment to provide a further reaction or detection chamber. The unused chamber 35 is also shown in FIGS. 3, 4 and 5.

[0252] FIG. 3 shows a schematic illustration of a microfluidic chip 1 according to an embodiment of the present invention. The illustration shows features, which would not necessarily be visible to the naked eye after fabrication of the microfluidic chip 1. In FIG. 3, fluidic channels, reaction chambers, detection chambers as well as inlet 2 and outlets 6 can be seen.

[0253] The fluidic channel(s) 7 are suitable for carrying at least a part of the fluid sample and each fluidic channel 7 is in fluid connection with an outlet 6 downstream from the inlet 2 thus allowing the received fluid sample to flow from the inlet 2 towards the outlet 6 of each fluidic channel. Each of the fluidic channel(s) 7 thus have a common inlet 2 for the fluid sample. A fluidic channel may be: [0254] straight, [0255] meandering, e.g. in a zig-zag shape 10, which facilitates mixing of the fluid sample, or [0256] intersecting, i.e. joining or splitting away from a fluid path from inlet 2 to outlet 6 [0257] a shape to facilitate a desired property of the fluidic channel.

[0258] By designing the fluidic components, i.e. the parts of the microfluidic chip 1, which come in contact with the fluid sample, such as e.g. inlet 2, outlet(s) 6, fluidic channels 7, chamber surfaces 8, 9, etc., to promote fluidic action, a microfluidic chip 1 will have a fluid flow that is solely powerless flow. By powerless is meant that no external power such as from a pump is necessary to cause the flow of the fluid sample in the microfluidic chip 1. The fluid sample may flow through the microfluidic chip 1 due to capillary flow, gravitational flow, air pressure, and the like.

[0259] In some embodiments, each reaction chamber may comprise at least one channel-specific reagent, i.e. a reagent for that part of the fluidic channel(s) and each detection chamber may comprise at least one detection chamber reagent. Such a detection chamber reagent may be imbedded or immobilized or loaded within the detection chamber. The detection chamber reagent may be selected to meet a specific need by consisting of a set of analyte-responsive elements, which will provide electromagnetic radiation, when the analyte is present in the fluid that reaches the detection chamber. Thus, a detection chamber reagent, but also a channel-specific reagent, may become activated if one or more analytes are present in the fluid sample. The activation will ideally result in electromagnetic radiation being emitted from the microfluidic chip 1 as a result of a reaction between the channel-specific reagent and/or a detection chamber reagent with the one or more analytes, if present.

[0260] In some embodiments, a channel-specific reagent is at least one of a micro-probe or a bioreceptor.

[0261] When a fluid sample is put into the inlet 2 of the microfluidic chip 1, the fluid flows through the fluidic channels 7 and any reaction chambers to reach the at least one detection chambers and here provide a detectable signal if the channel-specific reagent became activated. A reaction in a reaction chamber may cause electromagnetic radiation to be emitted, but ideally, the reaction chambers are where reagents, such as e.g. recognition molecules or reaction species, are located. Often these reagents only form intermediate products, while the one or more detection chambers are where dyes, enzymes, etc. react with the fluid sample to give off an electromagnetic signal for detection. The electromagnetic signal produced may be characterised as being either colorimetric or fluorimetric. A specific signal will usually be produced within a pre-determined time period. For example, a Nitrogen test signal is produced within a time period of 50 seconds, while a Potassium test produces an electromagnetic signal within 36 seconds.

[0262] In some embodiments, the microfluidic chip 1 comprises a plurality of reaction chambers. A microfluidic chip 1 may comprise several reaction chambers, possibly as many as twenty reaction chambers.

[0263] FIGS. 4 and 5 show a schematic illustration of a microfluidic chip 1 according to an embodiment of the present invention. The illustration shows features, which would not necessarily be visible to the naked eye after fabrication of the microfluidic chip. In FIG. 4 is shown an embodiment in which reaction chamber surfaces 8 and detection chamber surfaces 9 have been engraved with lines. The lines may be engraved with a laser. Such an engraved surface 14 along the fluid path through the microfluidic chip 1 may be used to manipulate the flow of the fluid, for instance, if the fluid has to react with a chemical in a slow manner.

[0264] A reaction chamber surface 8 and/or a detection chamber surface 9 may be modified by at least one of the processes of: [0265] laser patterning, [0266] chemical treatment, such as e.g. coating, immersion in a solvent, incubation in a solvent, and/or [0267] exposure to UV radiation.

[0268] By modifying a reaction chamber surface or detection chamber surface the affinity of the surface to accept binding of molecules may be increased. For example, a pattern created with e.g. a laser may allow for easier physical adsorption of molecules in the drying process. In an embodiment, at least one of the patterns engraved to provide a reaction chamber surface and/or a detection chamber surface increases the binding affinity for a reagent to be dispensed thereupon.

[0269] Engraving of a surface anywhere along the fluid path may be used to alter the fluid flow in that part of the fluid path. This is not shown in FIGS. 4 and 5, but will be similar to the method used for the reaction chamber surface(s) and detection chamber surface(s).

[0270] Thus, a part of or the whole of one or more of the fluidic channels may be engraved, e.g. by a laser, the engraving comprising a pattern and/or one or more lines in the direction of the fluid flow or one or more lines in a direction being at an angle to the direction of the fluid flow. When the one or more engraved lines are in the direction of the fluid flow, they may facilitate the flow of the fluid inside that part of the fluidic channel. When the one or more engraved lines are in a direction at an angle to the direction of the fluid flow the engraved lines may slow down the fluid as the fluid flows past the engraved part of the fluidic channel. Usually, the closer the angle between the lines and the direction of the fluid flow is to 90 degrees, i.e. the closer the lines are to being orthogonal to the direction of the fluid flow, the more the fluid flow will be slowed down.

[0271] FIG. 6A and 6B each show schematically an example of a plurality of layers used in embodiments of the present invention to fabricate a microfluidic chip. FIG. 6A shows three layers, which may be: a base layer 17, which also functions as reagent carrier layer, a fluidic channel layer 16 and a top layer 15. FIG. 6B shows four layers, which may be: a base layer 19, a reagent carrier layer 18, a fluidic channel layer 16 and a top layer 15.

[0272] If surface engraving of the base layer 17 and/or reagent carrier layer 18 would cause the release of reactive species from within the polymeric material, reaction and detection chambers may be formed by cutting or engraving structures in layers, which go on top of the base layer 17 and/or reagent carrier layer 18. A possibility is to cut a fluidic passage hole in a larger surface of at least one layer of the plurality of layers, whereby the fluidic passage hole cut-out will define a chamber surface on an adjacent layer after assembly of the plurality of layers.

[0273] In further embodiments, the microfluidic chip 1 may have fewer than three layers or more than four layers.

[0274] FIG. 7 shows schematically a side view of an analysis device 11. Visible in FIG. 7 is a barcode scanner 12 and a microfluidic chip inlet 13. The analysis device 11 may be used for analysing any electromagnetic radiation emitted from one or more detection chambers in a microfluidic chip 1. Such an analysis device will comprise: [0275] a barcode scanner 12, [0276] a microfluidic chip inlet 13, where the microfluidic chip inlet 13 is suitable for insertion of a microfluidic chip 1 into the analysis device 11, [0277] an optical sensor, [0278] a lens array, [0279] one or more light sources, [0280] an optical filter, [0281] a display screen, [0282] a power supplying element.

[0283] The barcode scanner 12 allows for information about a microfluidic chip 1 to be communicated to the analysis device 11 by scanning an identifier located on the microfluidic chip 1. The identifier may be an engraving on the microfluidic chip. The information communicated to the analysis device 11 by scanning of an identifier may comprise type of chip and what analytes the chip is suitable for detecting, which enables the analysis device 11 to recognize the field of analysis and therefore run a suitable specific algorithm for the analysis.

[0284] A microfluidic chip inlet 13 provides a suitable inlet for insertion of a microfluidic chip 1 into the analysis device 11. The size of the microfluidic chip inlet 13 and the fixture that aligns the microfluidic chip 1 with the optical sensor inside the analysis device 11 may be of varying shapes and sizes to allow for differently shaped microfluidic chips 1 to be inserted into the analysis system 11.

[0285] An optical sensor, such as a CMOS sensor, may be positioned in combination with a lens array and placed on a mechanical fixture that aligns it with the one or more detection chambers in the microfluidic chip 1 for correct signal transfer of electromagnetic radiation from the microfluidic chip 1 to the analysis device 11.

[0286] The microfluidic system may be suited for a specific type of analysis, whereby the microfluidic chip 1 will comprise a suitable set of channel-specific reagents and/or a suitable set of detection chamber reagents and the analysis device 11 will comprise a suitable set of components for the specific type of analysis.

[0287] One or more light sources may provide illumination, if necessary, for an optical sensor viewing the one or more detection chambers of the microfluidic chip 1. The appropriate use of one or more illumination sources depends on the chemical reaction produced and may be used to create contrast. For example: [0288] if the chemistry produces a pink, red or maroon colour, then a green LED can be used to create contrast, [0289] if blue colours are produced, a red LED can be used, while [0290] if fluorescence is produced, a UV LED can be used.

[0291] An optical filter blocks specific wavelengths of light from entering the optical sensor thereby filtering unwanted signals that may arise during analysis. One example of an applicable filter for an analysis device is an IR filter that blocks infrared light from entering the optical sensor.

[0292] The display screen may comprise be any suitable display technology, such as a capacitive LCD touch screen.

[0293] The analysis device 11 may function similar to many multichannel detector systems such as CCD, CMOS, photodiode, photomultiplier tubes and the like. The arrangement of light source(s) and detector(s) is fixed by a mechanical fixture, while the operational sequence of lighting and detection can be varied based on the application or use. Similarly, it is possible to combine more than one light sources or detectors to monitor different types of responses on sensor films, and then combine them in manners known in the prior art.

[0294] In some embodiments, the light sources are red (650 nm), green (600 nm), blue (420 nm) and UV (380 nm) intensities and the value of each pixel seen by the optical sensor is recorded in a digital file. The digital file may undergo transformations and processing to convert data into a usable form and combine with empirical data to produce a defined output. The analysis device 11 may use multiple LEDs of varying spectrums to irradiate the subject for the pixel intensity measurements. Colour response and grey scale response may be recorded in pixel points by the optical sensor. Any change in colour/fluorescence or change in intensity of colour/fluorescence of each pixel of the image taken of the at least one detection chamber is used to convert light data to concentration of the analyte.

[0295] The overall flow of signal processing of the analysis device may follow the sequence of: signal capture, signal manipulation, signal to data interpretation, data transformation, data comparison, result derivation and result display. The entirety of the flow may be completed on the analysis device itself or may be completed on separate processing units where the data at any stage may be uploaded via internet to processing units housed elsewhere.

[0296] FIG. 8 shows schematically a syringe 24 for use in providing a fluid sample 21 to the inlet 2 of a microfluidic chip 1. Such a syringe 24 may be used to pre-process the fluid sample 21, where the pre-processing may comprise mixing or dissolving of one or more reagents or other chemical additions, all of which is conducted in the column 20 of the syringe 24. A filter 22 may be added onto the syringe 24 prior to or after the pre-processing of the fluid sample 21 being completed. For testing of the fluid sample 21 using a microfluidic chip 1, a droplet of fluid sample 21 is generated through the filter 22 and dispensed on the microfluidic chip 1 from the opening of the filter 23 to the inlet 2 of a microfluidic chip 1.

[0297] FIG. 9 is a flow-chart of a method according to the invention. The flow chart describes a method of using a microfluidic chip 1. In the method example depicted, the fluid sample 21, prior to being administered at the inlet 2, is treated with an extraction liquid 25 in a syringe 2 with filter 22. The extraction liquid used to dissolve the test sample 21 may contain chemicals that assist the flow of the fluid sample in the microfluidic chip 1. The fluid sample 21 flows into the fluidic channels 7, passing any reaction chamber surfaces 8, and further into the detection chambers to contact the detection chamber surface 9, where emission of any electromagnetic radiation caused by a reaction between an analyte and one or more reagents can leave the microfluidic chip 1. After analysis of any electromagnetic radiation 26 or lack thereof by the analysis device 11, information is passed on to a user 27.

[0298] FIG. 10 is a flow-chart of a method according to the invention. The user interface 28 on the analysis device 11 can send input signals 36 to the processor unit 30, receive and display the output 29 from the processor unit 30. The processor unit 30 may have unidirectional or bidirectional communication with several elements including a sensor array 31, light source array 32, barcode scanner 12 and other peripheral devices such as a thermal printer 33. The communication of the processor unit 30 and the sensor array 31 and light source array 32 is the core functionality and may involve multiple passes of information to deliver a single result of the image data 34 to the user 27.

[0299] Although the present invention has been described in connection with the specified embodiments, it should not be construed as being in any way limited to the presented examples. The scope of the present invention is set out by the accompanying claim set. In the context of the claims, the terms “comprising” or “comprises” do not exclude other possible elements or steps. Also, the mentioning of references such as “a” or “an” etc. should not be construed as excluding a plurality. The use of reference signs in the claims with respect to elements indicated in the figures shall also not be construed as limiting the scope of the invention. Furthermore, individual features mentioned in different claims, may possibly be advantageously combined, and the mentioning of these features in different claims does not exclude that a combination of features is not possible and advantageous.

[0300] 1 microfluidic chip

[0301] 2 inlet

[0302] 3, 4, 5 layers in a plurality of layers

[0303] 6 outlet

[0304] 7 fluidic channel

[0305] 8 reaction chamber surface

[0306] 9 detection chamber surface

[0307] 10 zig-zag shaped fluidic channel

[0308] 11 analysis device

[0309] 12 barcode scanner

[0310] 13 microfluidic chip inlet

[0311] 14 engraved surface

[0312] 15 top/capping layer

[0313] 16 fluidic channel layer

[0314] 17 bottom/base+reagent carrier layer

[0315] 18 reagent carrier layer

[0316] 19 bottom/base layer

[0317] 20 column

[0318] 21 fluid sample

[0319] 22 filter

[0320] 23 filter opening

[0321] 24 syringe

[0322] 25 extraction liquid

[0323] 26 analysis of electromagnetic radiation

[0324] 27 user

[0325] 28 user interface

[0326] 29 output

[0327] 30 processor unit

[0328] 31 sensor array

[0329] 32 light source array

[0330] 33 thermal printer

[0331] 34 image data

[0332] 35 unused chamber

[0333] 36 input signals